E-cigarettes:
What Every Clinician Should Know
Jonathan D. Klein, MD, MPH, FAAP
American Academy of Pediatrics
Julius B. Richmond Center of Excellence
Society for Adolescent Health and Medicine
March, 2015
Objectives
• I have no conflicts of interest.
• I do not intend to but may discuss
unapproved use of a commercial product/deviceuse of Nicotine replacement therapy for smoking
cessation by young people under age 18.
Objectives – e-cigarettes and “vaping” devices
• Who is using them
• What are they
• Public and individual health concerns
–
–
–
–
–
Safety of devices/poisoning risk
Potential for adolescent nicotine addiction
Potential to glamourize and re-normalize smoking
Evidence for cessation/dual use
Evidence for effects of second-hand vapor exposure
E-cigarette Prevalence 2013
• 6.1% of youth (6-12 grades) had ever tried e-cigarette
– From NYTS 2013 - > 3x rate from 2011
– 20.2% of ever-cigarette smokers and 0.9% of never smokers
• Current US e-cigarette use
- 6.9% ever-smokers
- 0.3% never-smokers
• Utah -
5.9% current
• Hawaii - 29% ever
18% current
Bunnell et al. Nicotine and Tobacco Research, 2014; Wills, in press
Legacy US 2014 data
Ever and Current Use of E-Cigs
Trends in adult current use
of e-cigarettes 2010-2013
16
14
12
10
2010
8
2011
2012
6
2013
4
2
0
Overall
18-24 years
25-44 years
45-64 years
McMillen, et al. “Trends in electronic cigarette use among US adults. In press, 2014
65+ years
What are e-cigarettes?
www.vapeze.co.uk/what-are-electronic-cigarettes.html
Rachel Grana et al. Circulation. 2014;129:1972-1986
From Cigarette to
Vapor Pen:
evolving
technology
Constituents of “e-juice”:
humectant, flavoring, +/- nicotine
• GRAS classification:
– Generally recognized as safe for use IN FOOD
– Based on scientific evidence or use before 1958
• GRAS means safe for certain populations, in certain
quantities, for ingestion or topical use
• Have NOT been assessed for safety as inhalants
Constituents of e-juice: Humectants
• Propylene glycol: general recognized as safe
– Few human studies for inhalation, used as a tobacco
humectant historically
• Can cause eye and respiratory irritation
• Dow Chemical states “inhalation exposure to mists should be avoided”
• Altria published a study in rats and dogs in 2011, stating a plan to
conduct “first-time-in-man” human exposure studies
• Vegetable glycerin: generally recognized as safe
– When heated and vaporized, can form acrolein, which can
cause upper respiratory irritation
• Unknown long-term health effects
Werley et al, Toxicology 2011
Humectant Toxicity – heating creates
carcinogenic compounds
Kosmider et al, Nicotine & Tobacco Research 2014
www.nightclubshop.com
/e-hookah-section/
Constituents of e-juice: Nicotine
• Nicotine effects
– Complex pharmacodynamics – neural stimulant at low
doses and a depressant at high doses
• Stimulates memory and alertness. People who use tobacco often
depend on it to help accomplish certain tasks and perform well.
• Many people feel a sense of well-being.
• Decreases appetite (fear of weight gain affects some people's
willingness to stop smoking); may relieve minor depression.
• Increases intestinal activity, creates more saliva and phlegm,
increases heart rate by 10 to 20 beats per minute; increases blood
pressure by 5 to 10 mmHg.
Constituents of e-juice: Nicotine
• Nicotine overdose
– Excess: nausea and vomiting, excessive salivation,
abdominal pain, pallor, sweating, hypertension,
tachycardia, ataxia, tremor, headache, dizziness, muscle
fasiculations, and seizures
– Death: several case reports of suicide by nicotine
• Two child deaths SO FAR from e-juice reported
Nicotine Toxicity?
• The dose makes the poison
– Oral nicotine ~20% bioavailable
• Lethal dose
rats= 50mg/kg
mice 3mg/kg
• Humans? Stated as 0.8mg/kg (60mg)
– Multiple literature reports of survival at 6 mg/kg
– Recent review suggests LD50 = 6.5-13mg/kg
Archives of Toxicology, 2013
Mayer, Arch Toxicol 2014
18mg/ml is standard – 6 oz = 3280 mg
Toxic dose for 60kg person = 6.5-13mg/kg=6-12 ml
Poison Control Calls
Too late to save a life…
• December 9, 2014, EJ Hotaling, an
18 month old from upstate NY,
ingested nicotine refill solution
while his mother was turning on his
favorite TV show
• He seized and never regained
consciousness
• He is the first child to die in the US
from refillable nicotine
• NY Governor signed a nicotine
packaging bill into law on 12/29/14
Photos: Times Union, 12/30/14
Child Nicotine Poisoning Prevention Act of 2015
• Child Nicotine Poisoning Prevention Act of 2015 (S. 142)
– Re-introduced by Sen. Nelson (D-FL) and Sen. Ayotte (R-NH) and 10 other
Senators
– Grants Consumer Product Safety Commission (CPSC) authority to require
child-proof packaging for nicotine refill solutions sold to consumers
(current law prohibits CPSC from regulating any tobacco products)
– The bill is crafted narrowly to focus only on liquid nicotine and its safe
containment from children, and does not affect the manufacture of the
substance nor the products they are designed to refill
• 2/26/15: Bill passed Committee, sent to full Senate
• Awaiting action in House (Republican co-sponsor needed)
Nicotine and E-Cigarette Users…
• How much nicotine DO you get per puff?
– Different bioavailability through puffing than
drinking
– Depends on: temperature of the atomizer, how
much juice is atomized, droplet size, depth of the
“puff”, concentration of e-juice
• Large droplets deposit in the oropharynx and upper
airway (venous absorption)
• Small droplets get deeper – into alveoli for arterial
absorption
What are the health harms?
• Relative to smoked tobacco, less harmful
– No tar
– Variable levels of nicotine
• Relative to NO tobacco or medical NRT
– Growing concerns for decreased lung function (aldehydes)
– Quality control – adulterated products have been found
• Safety of flavor when heated and inhaled is unknown
• Non- and former smokers may become addicted
• May maintain combusted tobacco use
• Still completely unregulated
New Addiction?
• The adolescent brain appears uniquely susceptible to
nicotine addiction
• Animal studies show that nicotine exposure during
adolescence period has long-standing effects in the
brain including cell damage that leads to both
immediate and persistent behavior changes.
Slottkin, Neurotox & Teratol 2002
Cloud Vape Pen
Public Health Harms
• Second-hand vapor is NOT
just water vapor
– Emit variable levels of
nicotine (1/10th that of
cigarettes), plus fine particles
of similar size to that of
cigarettes, and comparable
concentration of fine
particles
– Emit low levels of other
toxins: formaldehyde,
acetaldehyde, metals
Czogala et al, Nicotine and Tobacco Research 2013
Fuoco et al, Environmental Pollution 2014
Surface Contamination
Nicotine on surfaces
from e-cigarette use
Combines with indoor
substances such as
ozone and nitrous oxide
to make irritants and
carcinogens (Tobacco
Specific Nitrosamines)
Goniewicz and Lee, Nicotine and Tobacco Research 2014
Second-hand e-vapor
Neonatal mice exposed to 1.8% E-cig
emissions twice a day for ten days
Serum nicotine
30
ppb
25
*
20
15
10
<5 ppb
<5 ppb
5
0
1 .8 % nicot ine
Air
0 % nicot ine
McGrrath-Morrow S, et al. PLoS One, Feb. 2015.
Room
Alveolar growth is impaired in newborn
mice exposed to E-cigarette emissions
Mean linear int ercept
( arbit rary unit s)
Room air
0% nicotine
80
1.8% nicotine
p=<0.001
70
p=<0.001
60
50
40
McGrrath-Morrow S, et al.
PLoS One, Feb. 2015
30
20
10
0
RA
0% Nicotine
1.8% Nicotine
Lung function is impaired
in neonatal mice exposed to
E-cigarette emissions
p<0.04
p<0.001
KI67 quantification
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Room Air
0% Nicotine
McGrrath-Morrow S, et al. PLoS One, Feb. 2015
1.8% Nicotine
Re-normalizing the image of smoking
–In places where smoking is not allowed
–Advertising is completely unrestricted
• TV ads for the first time since 1971
–Largely indistinguishable from
cigarettes
Why e-cigarettes/vape pen/e-hookah?
• Curiosity
• Reduction of other tobacco
products
• Cessation
• Stealth
• Perception of a safer
product
• Social acceptance
Vape Pen
Ploom
Marijuana Vaporizers
Is there evidence for e-cigarettes
for smoking cessation?
Very limited: most suggests that people
cut down and don’t stop completely…
Best Evidence for Cessation
(among those motivated to quit)
Brown et al. Addiction, 2014
Meta-analysis – Glantz et al 2015
11 studies = OR = 0.72 (95% CI 0.53- 0.98)
Smokers who use e-cigarettes
are about 30% less likely to quit
What happens now?
• Expected that the market will continue to explode
• Expected FDA jurisdiction – proposed rule April 2014
–
–
–
–
–
Improved quality control and production standards
No sales <18 years
Health warning labels
No vending machine sales
No marketing implying “healthy” or “safe”
• Final rule could come as early as June 2015
– Would go into effect 2 years AFTER final rule
– Misses several aspects: flavors, child-proof packaging,
marketing, online sales
E-Cigarette Laws by State
AAP Position – E-cigarettes
• Sales to youth should be prohibited
• Flavors should be banned
• Smoke free environments should include e-cigarettes
and their vapor inall workplace and clean air rules
• Child proof packaging should be required for E-liquids
--• Parent/child and adolescent prevention screening
and cessation counseling must ask the right
questions about e-cigs and secondhand vapor
So what should we do?
• Until we know more about “e-anything” and
cessation, recommend medicinal NRT, quit lines and
cessation support to tobacco/nicotine users
• Until there is regulation of marketing, flavoring, and
promotion to youth, “debate” over possible harm
reduction benefits of e-cigarettes supports industry
efforts to delay effective regulation and to create a
new generation addicted to nicotine
Thank you
www.aap.org /RichmondCenter